Revisional Surgery for Failed Gastric Restrictive Procedures for Morbid Obesity

As part of the Adelaide Obesity Surgery Study, we have reviewed all patients who have undergone revisional surgery. Of the 310 trial patients, 63 (20%) had revisions 1-69 (median 32) months following their original surgery--30% of all 105 gastrogastrostomy (GG) operations, 22% of 106 gastroplasty (GP) procedures, and 9% of 99 gastric bypasses (GB). Failure was due to stomal dilatation, 11% of all trial patients (71% of GG revisions), stomal stenosis, 6% (52% of GP revisions) and staple dehiscence, 4%. There was no mortality and a low hospital morbidity. Long-term success was only 23% (follow-up at least 3 years) and was achieved at considerable expense (3 reversals, 10 further revisions, 44 endoscopic procedures). Revisional surgery was successful in 45% of patients with stomal dilatation or dehiscence but in only 17% with stenosis. Overall, the most successful operation was revision of, or conversion to, gastric bypass (58% success rate), compared with gastroplasty (24%) and gastrogastrostomy (25%). Our long-term results following revisional surgery were disappointing, particularly for stenosis, and most failures followed revision to GG or GP. Roux-en-Y gastric bypass is the procedure of choice when considering revision.     

The Timothy syndrome mutation of cardiac CaV1.2 (L-type) channels: multiple altered gating mechanisms and pharmacological restoration of inactivation

Timothy syndrome (TS) is a multiorgan dysfunction caused by a Gly to Arg substitution at position 406 (G406R) of the human CaV1.2 (L-type) channel. The TS phenotype includes severe arrhythmias that are thought to be triggered by impaired open-state voltage-dependent inactivation (OS vd I). The effect of the TS mutation on other L-channel gating mechanisms has yet to be investigated. We compared kinetic properties of exogenously expressed (HEK293 cells) rabbit cardiac L-channels with (G436R; corresponding to position 406 in human clone) and without (wild-type) the TS mutation. Our results surprisingly show that the TS mutation did not affect close-state voltage-dependent inactivation, which suggests different gating mechanisms underlie these two types of voltage-dependent inactivation. The TS mutation also significantly slowed activation at voltages less than 10 mV, and significantly slowed deactivation across all test voltages. Deactivation was slowed in the double mutant G436R/S439A, which suggests that phosphorylation of S439 was not involved. The L-channel agonist Bay K8644 increased the magnitude of both step and tail currents, but surprisingly failed to slow deactivation of TS channels. Our mathematical model showed that slowed deactivation plus impaired OS vd I combine to synergistically increase cardiac action potential duration that is a likely cause of arrhythmias in TS patients. Roscovitine, a tri-substituted purine that enhances L-channel OS vd I, restored TS-impaired OS vd I. Thus, inactivation-enhancing drugs are likely to improve cardiac arrhythmias and other pathologies afflicting TS patients.     

National surveillance of occupational exposure to the human immunodeficiency virus

In September 1985, a prospective study was initiated to monitor the occurrence of occupational exposures to human immunodeficiency virus (HIV)-infected blood and body fluids in Canada. This program was coordinated by the Federal Centre for acquired immune deficiency syndrome (aids) (now the Division of HIV/aids Epidemiology at the Laboratory Centre for Disease Control). The objective was to determine the risk to workers of acquiring HIV infection as a result of exposure to HIV-infected blood and other body fluids. To be eligible, a worker must have sustained a documented parenteral, mucous membrane or skin contact exposure to blood or body fluids from an HIV-infected person. A baseline specimen was collected within a week of the exposure and then at six weeks, 12 weeks, six months and 12 months. Information concerning the type of exposure, precautions used and post exposure treatment was submitted to the Federal Centre for aids on standard data collection forms. All information was anonymous, identified only by a code number. Guidelines for counselling an exposed employee were provided with enrollment material. As of July 29, 1991, 414 employees have been included in the study. Two hundred and thirty-seven of the 414 exposures (57%) were needlestick injuries of which 167 (70%) were sustained by nurses. Other exposures consisted of open wound contamination, eye splashes, scalpel wounds and skin contact with blood and body fluids. To date, there have been no seroconversions among workers enrolled in the surveillance program.     

Analysis of GLRA1 in hereditary and sporadic hyperekplexia: a novel mutation in a family cosegregating for hyperekplexia and spastic paraparesis.

Hyperekplexia is a rare condition characterised by the presence of neonatal hypertonia and an exaggerated startle response. Mutations have been described in GLRA1, the gene encoding the alpha 1 subunit of the glycine receptor, in dominant families with hyperekplexia and in a single sporadic case, thought to represent an autosomal recessive form of the disease. In this study the coding region of the GLRA1 was analysed in eight probands with hyperekplexia by restriction digest and sequencing. Two familial cases were found to possess the previously described G1192A (R271Q) mutation in exon 6. In an additional family in which hyperekplexia cosegregates with spastic paraparesis, a novel A to G transversion at nucleotide 1206 in exon 6 was detected that changes a lysine at amino acid 276 to a glutamate (K276E). In four sporadic cases no mutations were found. In addition, one familial case did not have a mutation in the coding region of the gene.     

Effect of high Ba(2+) on norepinephrine-induced inhibition of N-type calcium current in bullfrog sympathetic neurons

The voltage-dependent inhibition of N-type calcium current by neurotransmitters is the best-understood example of neuronal calcium channel inhibition. One of the mechanisms by which this pathway is thought to inhibit the calcium current is by reducing the permeation of divalent cations through the channel. In this study one prediction of this hypothesis was examined, that high concentrations of divalent cations reduce the maximum neurotransmitter-induced inhibition. Norepinephrine (NE)-induced inhibition was compared in external solutions containing either 2 or 100 mM Ba(2+). Initially, NE dose-response curves were generated by averaging data from many neurons, and it was found that the relationship was right shifted in the high-Ba(2+) external solution without an effect on maximum inhibition. The IC(50) was 0.6 and 3 microM in 2 and 100 mM Ba(2+), respectively. This shift was verified by comparing the effect of NE on single neurons exposed to both 2 and 100 mM Ba(2+). The inhibition induced by 1 microM NE was reduced in 100 mM Ba(2+) compared with that in 2 mM Ba(2+). However, the response to 100 microM NE was identical between high and low Ba(2+). Thus, divalent cations appear to act as a competitive inhibitor of NE binding, which likely results from these ions' interacting with negatively charged amino acids that are important for catecholamine binding to adrenergic receptors. Because the maximum inhibition induced by NE was similar in low and high Ba(2+), the effect of inhibition on single N-type calcium channels was not altered by the divalent cation concentration.     

Geographic and birth cohort associations of Kaposi's sarcoma among homosexual men in Canada

The authors conducted an analysis of all 677 cases of Kaposi's sarcoma among the 3,047 cases of acquired immunodeficiency syndrome diagnosed in homosexual/bisexual men in Canada between 1980 and 1989. The proportion with Kaposi's sarcoma declined from 32.2% during 1980-1985 to 15.0% in 1989. The proportion with Kaposi's sarcoma was significantly higher in primary epidemic centers (Vancouver, Toronto, and Montreal) and in men in the 1945-1954 birth cohort independent of year of diagnosis. These data are consistent with an environmental cofactor for Kaposi's sarcoma which is likely to be a sexually transmitted agent.     

Psychosocial and physical activity changes after gastric restrictive procedures for morbid obesity

Gastric restrictive procedures for morbid obesity are frequently performed to reduce problems arising from the physical limitations and social isolation of massive obesity. Numerous reports have described changes in weight after gastric restrictive operations, yet few studies have documented changes in the secondary effects of obesity. This report deals with changes in psychosocial status and physical activity occurring in 240 patients who remained in the study 3 years after surgery. These patients were members of a group of 310 patients who were entered into a prospective randomized trial to assess the relative benefits of three forms of gastric restrictive procedure. Prior to operation, and at yearly intervals after operation, the physical activities and psychosocial status of each patient was assessed by a standardized semi-structured interview. At the time of the three-year interview the median weight loss for these patients was 29.5 kg which represents 53% of excess weight lost. This weight loss was associated with a marked reduction in the amount of food eaten. There was a significant increase in the number of patients smoking more than 20 cigarettes a day and a mild increase in alcohol intake. There were significant improvements in the level of self-image and state of happiness. The social lives and sex lives of the majority of patients were improved and a significantly greater number of patients reported being in a stable emotional relationship at 3 years after operation than did so pre-operatively. There was a marked increase in the number of patients in full-time or part-time employment from 38% prior to surgery to 60% at 3 years after operation.(ABSTRACT TRUNCATED AT 250 WORDS)